Medication Summary

Only antidepressants that potently inhibit presynaptic reuptake of serotonin appear to be effective in treating obsessive-compulsive disorder (OCD). Clomipramine (Anafranil) is the only tricyclic antidepressant (TCA) with this quality. The selective serotonin reuptake inhibitors (SSRIs) are also effective. SSRIs have the advantages of ease of dosing and low toxicity in overdose. Available SSRIs include fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and sertraline (Zoloft).

SSRIs or clomipramine should be advanced as tolerated to a therapeutic dose. Clinical response may take 6-10 weeks to become apparent. The clinician should review adequacy of dose, duration of therapy, and compliance before deciding that a medication is ineffective.

SSRIs are generally preferred over clomipramine in treating OCD. The adverse effect profiles of SSRIs are less prominent, so improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with TCAs; however, citalopram causes dose-dependent QT prolongation.
[36, 37] Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with mood disorder.

Antipsychotics, such as haloperidol, olanzapine, and risperidone, have been used with some success in augmenting SSRIs in patients with OCD, particularly in patients with comorbid Tourette disorder or other tic disorders.
[18]

A Cochrane review found some evidence of efficacy for quetiapine or risperidone as a general augmentation strategy (not specifically for those with comorbid tics).
[38] However, heterogeneity was noted in doses used and in response, and the number of subjects in these studies was generally small

The dual serotonin-norepinephrine reuptake inhibitor antidepressants (SNRIs) venlafaxine (Effexor) and duloxetine (Cymbalta) may also have efficacy in OCD, and they have safety and tolerability profiles comparable to those of the SSRIs. However, neither has yet been FDA-approved specifically for treatment of OCD.

Complications of pharmacologic treatment

Physicians are advised to be aware of the following information and to use appropriate caution when considering treatment with SSRIs in the pediatric population.

In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweighed the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appeared to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.

In October 2003, the FDA issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA asked that additional studies be performed, because suicidality occurred in treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.

Upon further analysis of pooled clinical trial data, suicidality was reportedly increased in children and adolescents being treated with SSRIs for depression (approximately 2% for those treated with placebo vs 4% for those on SSRIs, although no actual suicides occurred in either group). These clinical trials were unfortunately not designed to specifically and clearly assess suicidal thoughts and behaviors and therefore included events that were not readily classified.

The FDA issued a public health advisory in October of 2004
[39] mandating a black box warning for antidepressants. Antidepressant treatment of children and adolescents with depression then significantly decreased over the next 2 years, although apparently so did suicides for this population. In 2007, the FDA extended its warning to young adults.
[40]

Currently, evidence does not exist to associate an increased risk of suicide in patients with OCD and/or other anxiety disorders being treated with SSRIs. However, physicians should closely attend to whether treated patients have unusual, uncomfortable adverse reactions (eg, akathisia) or if they might have comorbid bipolar disorder (which may involve only subtle hypomanic episodes), as antidepressant use seems to occasionally be associated with triggering dysphoria and, sometimes, manic episodes in such individuals.

Children, adolescents, and young adults being treated with antidepressants should be closely and frequently monitored, particularly early in treatment, for any suicidal ideation or actions.

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Selective Serotonin Reuptake Inhibitors

Class Summary

First-line pharmacologic treatments consist of selective serotonin reuptake inhibitors (SSRIs). SSRIs have the advantages of ease of dosing and low toxicity in overdose. Available SSRIs include fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and sertraline (Zoloft). SSRIs are generally preferred over clomipramine in treating OCD. The adverse effect profiles of SSRIs are less prominent, so improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with TCAs, however, dose-dependent QT prolongation has been reported with citalopram. Because of the risk for QT prolongation, citalopram is contraindicated in individuals with congenital long QT syndrome and the dose should not exceed 40 mg/d.
[36, 37] Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with a mood disorder.

Fluoxetine selectively inhibits presynaptic serotonin reuptake with minimal or no effect in the reuptake of norepinephrine or dopamine. Selective serotonin inhibitors such as fluoxetine have less sedation, cardiovascular, and anticholinergic effects than the TCAs.

Citalopram enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. Citalopram is FDA approved for depression but has been used for the treatment of anxiety disorders. SSRIs are the antidepressants of choice due to minimal anticholinergic effects.

Fluvoxamine enhances serotonin activity by selective reuptake inhibition at the neuronal membrane. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than TCAs. It is FDA-approved for OCD in children (8-17 y) and adults.

Escitalopram is an SSRI and S-enantiomer of citalopram. Its mechanism of action is thought to be potentiation of serotonergic activity in the CNS, resulting from inhibition of CNS neuronal reuptake of serotonin.

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Tricyclic Antidepressants

Class Summary

Tricyclic are a class of antidepressants that work by inhibiting the reuptake of norepinephrine or serotonin at presynaptic neurons.

Clomipramine is FDA approved to treat obsessions and compulsions in OCD. It is a dibenzazepine compound belonging to family of TCAs. It inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Clomipramine affects serotonin uptake, while it affects norepinephrine uptake when converted into its metabolite desmethylclomipramine.

Desipramine is a TCA that has norepinephrine and serotonin reuptake-inhibition properties. It is not FDA approved for OCD; however, it has shown beneficial effects, especially when combined with SSRIs.

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Serotonin Norepinephrine Reuptake Inhibitor

Class Summary

The dual serotonin-norepinephrine reuptake inhibitor antidepressants (SNRIs) venlafaxine (Effexor) and duloxetine (Cymbalta) may also have efficacy in OCD, and they have safety and tolerability profiles comparable to those of the SSRIs. However, neither has yet been FDA approved specifically for the treatment of OCD.

Venlafaxine is a serotonin/norepinephrine reuptake inhibitor. It may treat depression by inhibiting neuronal serotonin and norepinephrine reuptake. In addition, it causes beta-receptor down-regulation. It is used in the treatment of OCD; however, it is not FDA approved for this indication.

Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake. Its antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in the CNS.

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Antipsychotic Agents

Class Summary

Antipsychotics, such as haloperidol, olanzapine, and risperidone, have been used with some success in augmenting SSRIs in patients with OCD, particularly in patients with comorbid Tourette disorder or other tic disorders. These agents are not FDA approved for the treatment of OCD but may be beneficial.

Risperidone is an atypical antipsychotic that has high affinity for both serotonergic and dopaminergic receptors. It also binds to alpha1-adrenergic receptors and, with lower affinity, to H1-histaminergic and alpha2-adrenergic receptors. It is approved to treat patients with bipolar mania, schizophrenia, and irritability associated with autistic disorder.

Olanzapine is an atypical antipsychotic agent approved for the treatment of bipolar disorder, schizophrenia, and treatment-resistant depression. It may be helpful in the treatment of OCD; however, it is not FDA approved for this indication.

Lithium is an antipsychotic agent that is indicated for bipolar disorder. It influences the reuptake of serotonin and/or norepinephrine at cell membranes. It has been used in the treatment of OCD; however, it is not FDA approved for this indication.

Antianxiety Agents

Class Summary

Buspirone is an antianxiety agent not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative or anxiolytic drugs. It is a 5-HT1 agonist with serotonergic neurotransmission and some dopaminergic effects in the CNS.

[Guideline] American Psychiatric Association Work Group on Obsessive-Compulsive Disorder. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. July 2007. 164(suppl):1-56. [Full Text].